MicroRNAs in neurodegenerative diseases: from molecular mechanisms to clinical biomarkers, detection methods and therapeutic strategies—advances and challenges
Une revue complète sur le rôle diagnostique et thérapeutique des microARNs dans les maladies neurodégénératives
Résumé
Neurodegenerative diseases (NDDs) pose significant challenges in early detection and treatment due to their complex pathophysiology and heterogeneous clinical presentations. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, have emerged as promising diagnostic biomarkers and therapeutic targets in NDDs. Pathological examination of affected tissues reveals early synaptic dysfunction, protein misfolding, and neuroinflammation occur prior to overt clinical symptoms, highlighting the importance of sensitive diagnostics approaches in prodromal stages. This review summarizes for researchers on the role of miRNAs in NDDs by examining their diagnostic potential in biofluids such as blood and cerebrospinal fluid, and their therapeutic applicability through inhibition or replacement strategies. Literature from peer-reviewed databases was assessed with a focus on recent advances in molecular detection platforms, computational modeling of miRNA–mRNA interactions, and preclinical/clinical investigations. More than 2600 human miRNAs have been identified, collectively regulating over half of mammalian protein-coding genes. Quantitative methodologies, particularly reverse transcription quantitative PCR (RT-qPCR), enable reliable miRNA profiling, facilitating early diagnosis and prognosis of NDDs. Therapeutic strategies, including antagomirs, mimics, sponges and viral or non-viral delivery systems, show promise in modulating disease pathways. However, significant challenges remain, including variability in miRNA extraction and quantification protocols, off-target effects, delivery barriers across the blood brain barrier and limited reproducibility across studies. MiRNAs represent a class of molecular tools with potential to transform diagnostics and therapeutics in NDDs. Future research should prioritize methodological standardization, validation in large multicenter cohorts, and improved computational approaches to elucidate miRNA-mediated regulatory networks in NDDs. Replication studies and translational research are essential harnessing the the full clinical utility of miRNAs in the management of Alzheimer disease, Parkinson disease and other NDDs.
Mots clés
- Biofluid biomarkers
- MicroRNA Neurodegenerative diseases Alzheimer's disease Parkinson's disease Huntington's disease Amyotrophic lateral sclerosis Diagnostic biomarkers MiRNA-based therapeutics Molecular diagnostics Gene regulation Biofluid biomarkers Delivery technologies Neuroinflammation RT-qPCR NGS Clinical translation
- Clinical translation
- NGS
- RT-qPCR
- Neuroinflammation
- Delivery technologies
- MicroRNA
- Gene regulation
- Molecular diagnostics
- MiRNA-based therapeutics
- Diagnostic biomarkers
- Amyotrophic lateral sclerosis
- Huntington's disease
- Parkinson's disease
- Alzheimer's disease
- Neurodegenerative diseases